Comparison of Fenofibrate vs. Pravastatin for Patients With HIV and Lipid Abnormalities

• A Prospective, Multicenter, Randomized Trial Comparing the Efficacy and Safety of Fenofibrate Versus Pravastatin in HIV-Infected Subjects With Lipid Abnormalities (ACTG 5087) (LbPeB9018)
  Authored by Judith Aberg, Robert Zackin, Scott Evans, Yijun Yang, Beverly Alston, W. Keith Henry, Marshall Glesby, Susan Brobst, Susan Owens, Carl Fichtenbaum
  View the original abstract

Hyperlipidemia is a commonly encountered problem in people with HIV, either as a result of HIV infection itself, its treatment, or an interaction between the two. Furthermore -- as deaths from HIV-related opportunistic infections continue to decline -- most clinicians now believe that the goals for cardiovascular disease risk reduction outlined by The National Cholesterol Education Program (NCEP) should be applied to those with HIV as well. This ACTG study compared two different pharmacologic treatment approaches to the management of elevated triglycerides and cholesterol.

Study subjects were eligible if they had fasting LDL-cholesterol levels greater than 130, triglycerides greater than 200, and were on combination antiretroviral therapy for more than six months. In a double-blind fashion, they were then randomized to receive either pravastatin 40 mg daily -- the statin drug with the fewest drug interactions -- or fenofibrate 200 mg daily -- an agent from a different lipid-lowering drug class with particular efficacy in triglyceride (TG) reduction. The desired endpoint was a composite of LDL, TG and HDL levels, taking into account other cardiac risk factors. Those participants who did not meet this goal by week 12 were offered combination treatment.

A total of 159 patients were enrolled, 80 to fenofibrate and 79 to pravastatin. The baseline CD4+ cell count was 442, with HIV RNA level of 1.7 log. Approximately half of the participants (85 overall) had two or more additional risk factors for cardiac disease.

Responses to treatment -- defined as meeting the NCEP goal -- are outlined below:

Although these differences were statistically significant (with pravastatin favored for LDL and fenofibrate for HDL and TG), 136 of the 159 patients failed to meet all the NCEP outlined goals of treatment by week 12, and were given combination therapy. This response rate was so low that the study was terminated early. There were no major safety issues, and, importantly, no cases of rhabdomyolysis, a known complication of statin therapy, especially when combined with a fibrate.

It is not known why HIV-related hyperlipidemia is so difficult to treat; potential explanations include direct drug effects (especially from the protease inhibitors), drug interactions, and host factors. Given the poor response to lipid-lowering therapy shown in this study, substitution strategies for an offending drug may be warranted if such options exist, especially in the presence of other known cardiac risk factors.